Background Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. Patients and methods This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at - 10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN). Results Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. Conclusions In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC.

中文翻译：

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一项III期随机研究，评估单剂量NEPA，netupitant和palonosetron的固定止吐药与预防性方案对接受高促发性化疗（HEC）的化疗引起的恶心和呕吐（CINV）的疗效。

背景技术需要联合使用多种抑制呕吐的分子途径的止吐药，以优化接受高度呕吐化疗（HEC）的患者的化疗诱导的恶心和呕吐（CINV）控制。NEPA是高度选择性的NK1受体拮抗剂，netupitant（300 mg）和药理学上不同的5-HT3RA palonosetron（PALO 0.50 mg）的固定组合，与PALO相比，在顺铂和蒽环类/环磷酰胺类药物中，CINV的预防效果优于PALO设置。这项研究是首次将NEPA与aprepitant（APR）/ granisetron（GRAN）方案进行头对头比较。患者和方法这是随机的，在亚洲进行的双盲III期研究的主要目的是证明未接受过顺铂类HEC的单纯化疗患者与3天口服APR / GRAN方案相比，单次口服NEPA的非劣效性。所有患者在第1-4天也接受了口服地塞米松（DEX）。主要功效终点是整个（0-120小时）阶段的完全缓解（CR：无呕吐/无急救药物）。非劣效性定义为低于非劣质性边缘设定为-10％的较低的95％CI。次要疗效终点包括无呕吐，无急救药物和无明显恶心（NSN）。结果治疗组在分析的828例患者中具有可比性：主要是男性（71％）；平均年龄54.5岁；ECOG 0-1（98％）；肺癌（58％）。NEPA的总体CR表现不逊于APR / GRAN [NEPA 73.8％，APR / GRAN 72.4％，95％CI（-4.5％，7.5％）]。无呕吐[NEPA 75.0％对APR / GRAN 74.0％，95％CI（-4.8％，6.9％）]和NSN率[NEPA 75.7％对APR / GRAN 70.4％，95％CI（-0.6％，11.4％）两组之间的相似]，但明显更多的NEPA患者未服用急救药物[NEPA 96.6％，APR / GRAN 93.5％，95％CI（0.2％，6.1％）]。NEPA具有良好的耐受性，其安全性与APR / GRAN相似。结论在比较NK1RA方案和DEX的第一项研究中，仅在第1天施用NEPA就不超过3天的口服APR / GRAN方案在预防与HEC相关的CINV方面。两组之间相似，分别为6％，11.4％）]，但明显更多的NEPA患者未服用急救药物[NEPA 96.6％与APR / GRAN 93.5％，95％CI（0.2％，6.1％）]。NEPA具有良好的耐受性，其安全性与APR / GRAN相似。结论在比较NK1RA方案和DEX的第一项研究中，仅在第1天施用NEPA就不超过3天的口服APR / GRAN方案在预防与HEC相关的CINV方面。两组之间相似，分别为6％，11.4％）]，但明显更多的NEPA患者未服用急救药物[NEPA 96.6％与APR / GRAN 93.5％，95％CI（0.2％，6.1％）]。NEPA具有良好的耐受性，其安全性与APR / GRAN相似。结论在比较NK1RA方案和DEX的第一项研究中，仅在第1天施用NEPA就不超过3天的口服APR / GRAN方案在预防与HEC相关的CINV方面。